Evidence for extensive elimination of cells during postnatal pancreas growth

It is typically assumed that normal postnatal growth is an efficient process in which cell proliferation leads to increased cell number and tissue mass, with a minor participation of programmed cell death.

Using accurate measurements of cell size and organ mass in the pancreas of newborn and adult mammals we have estimated the number of pancreatic cells during postnatal growth. Pancreatic cell number is mice increases 2.5 fold from birth to adult life, due to a major contribution of cellular hypertrophy. Pancreatic cell number in human increases 3fold during the first year of life.

Strikingly, multiple independent approaches for assessing cell proliferation predict much more extensive growth than observed. For example, immunostaining for markers of proliferating cells (Ki67, PCNA&PHH3) in humans between birth and 1year predict cell number at one year that is orders of magnitude larger than observed. Immunostaining analysis of the mouse pancreas gives similar results. Genetic pulse-chase lineage tracing experiments in mice suggest that individual labeled cells give rise to clones with average size that far exceed the actual growth in organ size. Furthermore, reanalysis of heavy isotope labeling data reveals label dilution that also predicts massive expansion of the pancreas, beyond the actual growth observed. Classical markers of programmed cell death such as TUNEL and activated caspase3 reveal only exceedingly rare signals. To reconcile these discrepancies, we propose that postnatal growth of the pancreas – and presumably other organs- involves massive loss of cells, which results in slow growth despite extensive DNA synthesis and cell cycling.